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Rituximab, Ifosfamide, Carboplatin, and Etoposide (RICE) Followed by Gallium Nitrate, Rituximab and Dexamethasone (GARD) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Primary Purpose

Diffuse Large B-cell Lymphoma

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
RICE
GaRD Treatment
Sponsored by
Loyola University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-cell Lymphoma focused on measuring CARBOPLATIN, DEXAMETHASONE, DIFFUSE LARGE B-CELL LYMPHOMA, ETOPOSIDE, GALLIUM NITRATE, IFOSFAMIDE, PHASE II, RELAPSED OR REFRACTORY, RITUXIMAB

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Must have histologically or cytologically confirmed diffuse, large B-cell lymphoma (WHO classification diffuse large B-cell lymphoma or mediastinal large B-cell lymphoma), immunoblastic B cell lymphoma or Burkitts lymphoma. Transformed, large B-cell lymphoma will be excluded.
  • Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm with spiral CT scan.
  • Must be refractory to initial therapy or have disease relapse from prior therapy and must be at least 3 weeks post treatment from prior chemotherapy or radiation therapy.
  • Age >18 years.
  • Life expectancy >24 weeks
  • SWOG performance status <1 (Karnofsky >80%).

  • Must have normal organ function (or impaired marrow function) as defined below:

    • leukocytes > or equal to 1,500/mcL
    • absolute neutrophil count >or equal to 1,000/mcL
    • platelets >or equal to 50,000/mcL
    • total bilirubin within normal institutional limits
    • AST(SGOT)/ALT(SGPT)<or equal to 2.5 X institutional upper limit of normal unless due to lymphoma involvement
    • creatinine clearance > than or equal to 60 mL/min
  • Must agree not to become pregnant for the duration of study participation.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
  • Follicular B-cell lymphomas, small lymphocytic lymphomas, chronic lymphocytic leukemia, lymphoblastic lymphomas and all T-cell lymphomas.
  • Patients may not be receiving any other investigational agents, within trials in the previous 4 weeks.
  • Patients with known CNS metastases are excluded from this clinical trial.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to gallium nitrate, rituximab, dexamethasone, ifosfamide, carboplatin, and/or etoposide.
  • Prior therapy with gallium nitrate, ifosfamide, carboplatin and/or etoposide
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant and women who are nursing are excluded from this study.
  • Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with RICE and/or GaRD.

Sites / Locations

  • Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RICE followed by GARD

Arm Description

RICE treatment: Rituximab by intravenous infusion over 6-8 hours on day 1, Eptoposide by intravenous infusion over 2 hours on day 3-5, a 1-hour infusion of Carboplatin on day 4 and a 24-hour infusion of Ifosfamide on day 4, for 3 cycles. GaRD treatment: After RICE treatment, gallium nitrate will be given continuously over a 7 day period. In addition rituximab will be given on day 1 of each cycle. Dexamethasone will be given for the first 4 days of each cycle. The length of each cycle is 21 days.

Outcomes

Primary Outcome Measures

To determine CR rates of standard salvage chemotherapy with rituximab, ifosfamide, carboplatin and etoposide (RICE) for relapsed/refractory diffuse aggressive NHL followed by a novel regimen of gallium nitrate, rituximab, and dexamethasone (GARD)

Secondary Outcome Measures

To determine progression-free survival and overall survival following an autologous stem cell transplant performed after the completion of the above regimen, as well as assessment of stem cell collection.
To determine the toxicities of the regimen
To investigate in vitro assays that may predict response to gallium based salvage chemotherapy

Full Information

First Posted
February 3, 2009
Last Updated
March 14, 2016
Sponsor
Loyola University
Collaborators
Genta Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT00836173
Brief Title
Rituximab, Ifosfamide, Carboplatin, and Etoposide (RICE) Followed by Gallium Nitrate, Rituximab and Dexamethasone (GARD) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Official Title
A Phase II Study Evaluating Three Cyslces of Ifosfamide, Carboplatin, Etoposide, and Rituximab (RICE) Followed by Two Cycles of Gallium Nitrate, Rituximab and Dexamethasone (GARD) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma MA
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Withdrawn
Why Stopped
Gallium is no longer available for the conduct of this study.
Study Start Date
July 2008 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
May 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Loyola University
Collaborators
Genta Incorporated

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to find out what effects, good and/or bad; rituximab, ifosfamide, carboplatin and etoposide (RICE) followed by gallium nitrate, rituximab and dexamethasone (GARD) have on diffuse large B cell lymphoma. This research is being done to try to find a more effective treatment for this type of cancer. We want to know whether treatment with rituximab, ifosfamide, carboplatin and etoposide (RICE) then followed by gallium nitrate, rituximab and dexamethasone (GARD) will improve survival. Rituximab, ifosfamide, carboplatin and etoposide (RICE) are part of the usual treatment for diffuse large B-cell lymphoma. Gallium nitrate, rituximab and dexamethasone (GARD) in lymphoma is experimental.
Detailed Description
This is a Phase 2 trial evaluating the efficacy of adding the combination of GaRD x 2 cycles following 3 cycles of the standard salvage regimen of RICE for the treatment of relapsed or refractory diffuse, large B-cell lymphoma (DLBCL). The study will include patients who have relapsed after 1 prior treatment regimen or who are refractory to initial chemotherapy. We will evaluate patients for response rate (both partial and complete), toxicities, as well as overall and progression free survival. Eligible patients will receive standard RICE x 3 cycles followed by GaRD x 2 cycles. Patients who would otherwise be eligible, may then proceed to autologous stem cell transplant (ASCT).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-cell Lymphoma
Keywords
CARBOPLATIN, DEXAMETHASONE, DIFFUSE LARGE B-CELL LYMPHOMA, ETOPOSIDE, GALLIUM NITRATE, IFOSFAMIDE, PHASE II, RELAPSED OR REFRACTORY, RITUXIMAB

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RICE followed by GARD
Arm Type
Experimental
Arm Description
RICE treatment: Rituximab by intravenous infusion over 6-8 hours on day 1, Eptoposide by intravenous infusion over 2 hours on day 3-5, a 1-hour infusion of Carboplatin on day 4 and a 24-hour infusion of Ifosfamide on day 4, for 3 cycles. GaRD treatment: After RICE treatment, gallium nitrate will be given continuously over a 7 day period. In addition rituximab will be given on day 1 of each cycle. Dexamethasone will be given for the first 4 days of each cycle. The length of each cycle is 21 days.
Intervention Type
Drug
Intervention Name(s)
RICE
Intervention Description
RICE treatment: Rituximab by intravenous infusion over 6-8 hours on day 1, Eptoposide by intravenous infusion over 2 hours on day 3-5, a 1-hour infusion of Carboplatin on day 4 and a 24-hour infusion of Ifosfamide on day 4, each cycle is 14 days (2 weeks). Patients will receive 3 cycles of RICE treatment.
Intervention Type
Drug
Intervention Name(s)
GaRD Treatment
Intervention Description
After RICE treatment, patients will have gallium nitrate IV through a vein continuously over a 7 day period. Patients will also receive rituximab by intravenous infusion over a 3-6 hour period on day 1 of each cycle. Dexamethasone will be given as pills to be taken for 4 days in a row on the first 4 days of each cycle. The length of each cycle is 21 days (3 weeks). All patients will have 2 cycles of GaRD.
Primary Outcome Measure Information:
Title
To determine CR rates of standard salvage chemotherapy with rituximab, ifosfamide, carboplatin and etoposide (RICE) for relapsed/refractory diffuse aggressive NHL followed by a novel regimen of gallium nitrate, rituximab, and dexamethasone (GARD)
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
To determine progression-free survival and overall survival following an autologous stem cell transplant performed after the completion of the above regimen, as well as assessment of stem cell collection.
Time Frame
18 months
Title
To determine the toxicities of the regimen
Time Frame
approximately 12 weeks
Title
To investigate in vitro assays that may predict response to gallium based salvage chemotherapy
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Must have histologically or cytologically confirmed diffuse, large B-cell lymphoma (WHO classification diffuse large B-cell lymphoma or mediastinal large B-cell lymphoma), immunoblastic B cell lymphoma or Burkitts lymphoma. Transformed, large B-cell lymphoma will be excluded. Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm with spiral CT scan. Must be refractory to initial therapy or have disease relapse from prior therapy and must be at least 3 weeks post treatment from prior chemotherapy or radiation therapy. Age >18 years. Life expectancy >24 weeks SWOG performance status <1 (Karnofsky >80%). Must have normal organ function (or impaired marrow function) as defined below: leukocytes > or equal to 1,500/mcL absolute neutrophil count >or equal to 1,000/mcL platelets >or equal to 50,000/mcL total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT)<or equal to 2.5 X institutional upper limit of normal unless due to lymphoma involvement creatinine clearance > than or equal to 60 mL/min Must agree not to become pregnant for the duration of study participation. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. Follicular B-cell lymphomas, small lymphocytic lymphomas, chronic lymphocytic leukemia, lymphoblastic lymphomas and all T-cell lymphomas. Patients may not be receiving any other investigational agents, within trials in the previous 4 weeks. Patients with known CNS metastases are excluded from this clinical trial. History of allergic reactions attributed to compounds of similar chemical or biologic composition to gallium nitrate, rituximab, dexamethasone, ifosfamide, carboplatin, and/or etoposide. Prior therapy with gallium nitrate, ifosfamide, carboplatin and/or etoposide Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant and women who are nursing are excluded from this study. Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with RICE and/or GaRD.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott Smith, MD, PhD, FACP
Organizational Affiliation
Loyola University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Rituximab, Ifosfamide, Carboplatin, and Etoposide (RICE) Followed by Gallium Nitrate, Rituximab and Dexamethasone (GARD) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma

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